Although the sequence of morphological and biochemical changes associated with differentiation has been well delineated, the regulatory mechanisms which cause cells to differentiate are poorly understood. The long-term goal of the proposed studies is to increase our understanding of the process of cell specialization. For this purpose, methods which will induce the expression of differentiated functions in cells which do not possess these functions will be developed. The approach involves the use of heterokaryons formed by fusion of chick or rat skeletal muscle to human fibroblasts or amniotic cells. Optimal conditions for the induction of expression of inactive muscle genes will be defined and the potential to activate muscle functions will be followed as a function of muscle developmental stage. Species-specific muscle gene products will be systematically quantitated by photometry in order to test the putative role of activators and repressors in the muscle differentiative process. A prime objective of the proposed studies is to develop a system which will permit amniotic fluid cells to be used for the study of differentiated muscle functions. The heterokaryon system described should serve as a model approach to the prenatal diagnosis of a number of human genetic diseases characterized by aberrant differentiative functions not ordinarily expressed in amniotic cells.